Rituximab is a drug in the cytostatic drug class. It is a monoclonal antibody used primarily in the treatment of malignant lymphoma.
What is rituximab?
Rituximab was developed in the 1990s by Lee Nadler at Dana-Farber Cancer Institute. It was the first antibody approved for the treatment of cancer worldwide. In the EU, rituximab is marketed by Roche under the trade name MabThera. The biotechnologically produced drug is used in the EU primarily for cancer immunotherapy. However, it is also approved for the treatment of autoimmune diseases. Side effects occur quite frequently when taking rituximab. For example, more than half of cancer patients experience fever, skin rashes or breathing difficulties. The substance is better tolerated by patients with rheumatoid arthritis. Severe side effects such as Stevens-Johnson syndrome or toxic epidermal necrolysis occur rather rarely.
Pharmacologic effects
Rituximab is a monoclonal antibody. The IgG-kappa immunoglobulin is directed against the surface antigen CD20. This surface antigen is found largely on the surface of B lymphocytes. CD20 is found in almost all B-cell neoplasms. The use of rituximab in cancer is only useful if the cancer cells have the surface molecule CD20. In these cells, rituximab binds to CD20. This creates a complex that mobilizes the body’s own immune response. The destruction of the expressing cells is initiated via three different mechanisms of action. First, programmed cell death (apoptosis) is initiated in the affected cells. In this process, the cells first detach from the tissue association. They become increasingly eosinophilic and smaller. Vesicles form on the cell membrane. The cell nucleus also becomes increasingly dense and smaller. At the end of apoptosis, a small apoptotic corpuscle remains, which is removed by phagocytosis. In programmed cell death, there is no inflammatory response. In addition to apoptosis, complement-dependent B-cell lysis also develops. In this process, the various factors of complement react. The complement system is a cascade-like system of plasma proteins. At the end of the cascade, these trigger an antibody response in which the affected cells are attacked. This is followed by an inflammatory response with eventual destruction of the cells. The third mechanism of action is based on antibody-dependent cellular cytotoxicity. Rituximab attracts macrophages, granulocytes, and natural killer T cells, which eliminate the affected cells.
Medical application and use
Rituximab is mainly used to treat cancer. The drug is part of the standard therapy for low-grade malignant and follicular non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphomas are all malignancies of the lymphatic system that are not Hodgkin’s disease. The lymphomas are manifested by non-painful lymph node enlargement, fatigue, weight loss, fever, night sweats, or increased susceptibility to infection. Rituximab is usually combined with conventional chemotherapy in these cases. The CHOP regimen is frequently used. It includes the drugs cyclophosphamide, daunorubicin, vincristine, and prednisolone. Studies show that combining the CHOP protocol with rituximab has a favorable impact on prognosis. Rituximab is also one of the most important drugs for the treatment of transplant-associated lymphoma. These are lymphoma-like malignancies that occur after organ or stem cell transplantation. Rituximab is also used in combination with the drug bendamustine to treat advanced chronic lymphocytic leukemia. However, recent studies indicate that treatment outcomes improve when rituximab is combined with cyclophosphamide and fludarabine. When standard drugs and the initial TNF-α inhibitor fail, rituximab is also used to treat rheumatoid arthritis. Rheumatoid arthritis is a chronic inflammation of the joints, formerly also called chronic polyarthritis. Most often, the finger joints are affected. In many patients, two infusions within two weeks can achieve a good improvement in symptoms over a period of one year. A therapy interval of six months is recommended.Further infusions may maintain or improve treatment success. Another indication for the use of rituximab is membranous glomerulonephritis. This chronic inflammatory disease of the renal corpuscles is due to antibody formation against the proteins of kidney cells.
Risks and side effects
In oncology, more than 50 percent of patients develop adverse effects. These include fever, difficulty breathing, skin rashes, and chills. The severe symptoms are thought to be caused by the mass decay of destroyed cancer cells. During this decay, many cytokines are released. Cytokines are proteins that play an important role in immunological reactions and in inflammatory processes. The symptoms that result from the decay are therefore also summarized under the term cytokine release syndrome. The syndrome occurs mainly in patients with a large tumor mass. In the course of treatment, these side effects usually improve. In individual cancer patients, progressive multifocal leukoencephalopathy (PML) may develop during the course of treatment. In this case, the brain is affected by the JC virus due to immunodeficiency. The opportunistic viral infection is always fatal. The majority of PML cases occur in patients with lymph node cancer and concurrent treatment with immunosuppressive cytostatic drugs. PML cases have also been reported in patients with autoimmune diseases. Serious adverse events such as Stevens-Johnson syndrome and toxic epidermal necrolysis occur in less than 0.01 percent of treated patients.
